1.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
2.Consideration for Coronavirus Disease 2019 Drug Treatment in Patients with Epilepsy on Antiepileptic Drugs
Jung-Ick BYUN ; Jun-Sang SUNWOO ; Kyung Wook KANG ; Keun Tae KIM ; Daeyoung KIM ; Dong Wook KIM ; Saeyoon KIM ; Se Hee KIM ; Woojun KIM ; Hye-Jin MOON ; Hea Ree PARK ; Jong-Geun SEO ; Min Kyung CHU ; Kyoung Jin HWANG ; Dae-Won SEO ;
Journal of the Korean Neurological Association 2022;40(2):121-126
Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.
3.Prevalence and Public Awareness of Sleep Apnea Syndrome in South Korea
Keun Tae KIM ; Hea Ree PARK ; Jae Wook CHO ; Jee Hyun KIM ; Su-Hyun HAN ; Hye-jin MOON ; Seo-Yong LEE ; Yong Won CHO ;
Journal of Sleep Medicine 2022;19(3):133-138
Objectives:
In South Korea, a significant number of patients with obstructive sleep apnea have benefited from the insured continuous positive pressure for sleep apnea as of 2018. However, there is limited information on public awareness of sleep apnea syndrome in the country. A nationwide survey was conducted to evaluate the current status of public awareness on the diagnosis and treatment of sleep apnea.
Methods:
We conducted an online survey using structured questionnaires on symptoms and knowledge of diagnosis and treatment modalities for sleep apnea. A total of 4,000 participants aged 21 to 69 were proportionally allocated according to the residential area, gender, and age group.
Results:
The STOP questionnaire, a screening tool for sleep apnea, revealed that 1,044 (21.6%) scored ≥2 points, 327 (8.1%) scored ≥3 points, and 64 (1.6%) scored 4 points. However, only 19 of the 1,044 patients were being treated for sleep apnea, and 13 had been using continuous positive airway pressure. For the diagnosis of sleep apnea, 1,318 participants (33.0%) responded that polysomnography was necessary. For sleep apnea treatment, 1,954 (48.9%) participants responded that lifestyle modification was the treatment of choice, while 1,036 (25.9%) chose continuous positive pressure.
Conclusions
Although one-fifth were at high risk for sleep apnea, this disorder is still underestimated. Therefore, publicity and support are needed to improve public awareness of sleep apnea.
4.Renal Infarction in Vascular Ehlers-Danlos Syndrome
Hea Ran LEE ; Si Chan KIM ; Eun Hye YANG ; Su Yun JUNG ; Jai Won CHANG ; Eun Kyoung LEE
Korean Journal of Medicine 2022;97(4):271-276
Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the COL3A1 gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.
5.The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway
Hyeon Hui KANG ; In Kyoung KIM ; Chang Dong YEO ; Sei Won KIM ; Hea Yon LEE ; Jeong Hyeon IM ; Hee Young KWON ; Sang Haak LEE
Tuberculosis and Respiratory Diseases 2020;83(Supple 1):S63-S74
Background:
Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury.
Methods:
Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks.
Results:
In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased.
Conclusion
CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.
6.The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway
Hyeon Hui KANG ; In Kyoung KIM ; Chang Dong YEO ; Sei Won KIM ; Hea Yon LEE ; Jeong Hyeon IM ; Hee Young KWON ; Sang Haak LEE
Tuberculosis and Respiratory Diseases 2020;83(Supple 1):S63-S74
Background:
Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury.
Methods:
Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks.
Results:
In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased.
Conclusion
CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.
7.Characteristics of Faecal Microbiota in Korean Patients with Clostridioides difficile-associated Diarrhea
Yong Duk JEON ; Hea Won ANN ; Woon Ji LEE ; Jun Hyoung KIM ; Hye SEONG ; Jung Ho KIM ; Jin Young AHN ; Su Jin JEONG ; Nam Su KU ; Joon Sup YEOM ; Dongeun YONG ; Kyungwon LEE ; Jun Yong CHOI
Infection and Chemotherapy 2019;51(4):365-375
BACKGROUND:
The intestinal microbiota plays an important role in the pathogenesis of Clostridioides difficile-associated diarrhea, and regional and racial characteristics influence the microbiome composition and diversity. We investigated the intestinal microbiome characteristics of patients with C. difficile colitis (CD+) compared to those of patients with colitis not due to C. difficile (CD−), patients with vancomycin-resistant enterococci (VRE) colonization, and healthy controls, in Korea.
MATERIALS AND METHODS:
We collected stool samples from 24, 18, 11 and 13 subjects within CD+, CD−, VRE and healthy control groups, respectively. The microbial communities were evaluated by 454-pyrosequencing of bacterial 16s rRNA.
RESULTS:
The species richness and microbial diversity were significantly lower in the CD+ group compared to those in healthy controls, but not compared to those in CD− and VRE groups. Phylum-level analysis showed that the proportion of Actinobacteria in the CD+ group was significantly lower than in the healthy control, but was unchanged compared to that in CD− and VRE groups. At the genus level, compared to the healthy group, the CD+ group showed significantly lower proportions of Blautia, Bifidobacterium, Faecalibacterium et al. Compared to the VRE group, the CD+ group showed a significantly higher proportion of Anaerostipes.
CONCLUSIONS
We could identify the intestinal microbiome characteristics of Koreans with C. difficile colitis. It might help to develop microbiome based diagnostic and treatment modalities.
8.A Case Report: Total Parathyroidectomy with Autotransplantation for Secondary Hyperparathyroidism
Sung Hoon KIM ; Da Hea SEO ; Seun Deuk HWANG ; Ji Won KIM
International Journal of Thyroidology 2019;12(1):54-57
Secondary hyperparathyroidism (HPT) usually result from parathyroid gland hyperplasia that produces excess parathyroid hormone (PTH). Decreased renal function leads to elevate serum phosphate levels and reduce vitamin D production, which results in hypocalcemia. Skeletal resistance to PTH results in persistently and frequently extremely elevated PTH levels and renal osteopathy. Treatment of choice for secondary HPT is medical management including calcitriol and vitamin D. However, for some cases in calciphylaxis and the failure including PTH >800 pg/mL or osteoporosis under maximal medical management surgical intervention could be an alternative option. We described a case of 47-year-old woman with surgical intervention for secondary hyperparathyroidism.
Autografts
;
Calciphylaxis
;
Calcitriol
;
Female
;
Humans
;
Hyperparathyroidism, Secondary
;
Hyperplasia
;
Hypocalcemia
;
Middle Aged
;
Osteoporosis
;
Parathyroid Glands
;
Parathyroid Hormone
;
Parathyroidectomy
;
Transplantation, Autologous
;
Vitamin D
9.Effects of Early Exercise Rehabilitation on Functional Recovery in Patients with Severe Sepsis.
Jin Young AHN ; Je Eun SONG ; Hea Won ANN ; Yongduk JEON ; Mi Young AHN ; In Young JUNG ; Moo Hyun KIM ; Wooyoung JEONG ; Su Jin JEONG ; Nam Su KU ; June Myung KIM ; Sungwon NA ; Sung Rae CHO ; Jun Yong CHOI
Yonsei Medical Journal 2018;59(7):843-851
PURPOSE: Severe sepsis is associated with functional disability among patients surviving an acute phase of infection. Efforts to improve functional impairment are important. We assessed the effects of early exercise rehabilitation on functional outcomes in patients with severe sepsis. MATERIALS AND METHODS: A prospective, single-center, case-control study was conducted between January 2013 and May 2014 at a tertiary care center in Korea. Patients with severe sepsis and septic shock were enrolled and randomized to receive standard sepsis treatment or intervention. Intervention involved early targeted physical rehabilitation with sepsis treatment during hospitalization. Participants were assessed at enrollment, hospital discharge, and 6 months after enrollment. Functional recovery was measured using the Modified Barthel Index (MBI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL). RESULTS: Forty participants (21 intervention patients) were included in an intention-to-treat analysis. There were no significant differences in baseline MBI, FIM, and IADL between groups. Intervention yielded greater improvement of MBI, FIM, and IADL in the intervention group at hospital discharge, but not significantly. Subgroup analysis of patients with APACHE II scores ≥10 showed significantly greater improvement of physical function at hospital discharge (MBI and FIM) in the intervention group, compared to the control group (55.13 vs. 31.75, p=0.048; 52.40 vs. 31.25, p=0.045). Intervention was significantly associated with improvement of MBI in multiple linear regression analysis (standardized coefficient 0.358, p=0.048). CONCLUSION: Early physical rehabilitation may improve functional recovery at hospital discharge, especially in patients with high initial severity scores.
Activities of Daily Living
;
APACHE
;
Case-Control Studies
;
Hospitalization
;
Humans
;
Korea
;
Linear Models
;
Prospective Studies
;
Rehabilitation*
;
Sepsis*
;
Shock, Septic
;
Tertiary Care Centers
10.The factors associated with Vitamin D deficiency in community dwelling elderly in Korea.
Sun Hea KIM ; Jung Eun OH ; Dong Won SONG ; Choo Yon CHO ; Sung Ho HONG ; Yong Jin CHO ; Byung Wook YOO ; Kyung Suk SHIN ; Hyun JOE ; Hwang Sik SHIN ; Doo Yong SON
Nutrition Research and Practice 2018;12(5):387-395
BACKGROUND/OBJECTIVES: Recent studies showed vitamin D deficiency is linked to chronic diseases in addition to skeletal metabolism which could threaten the elderly. We analyzed health conditions and socio-demographic factors associated with vitamin D deficiency in community dwelling people aged 65 years and older. SUBJECTS/METHOD: Data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 to 2012 were obtained. A total of 2,687 subjects aged 65 years and older were participated. The cutoff value of the Vitamin D deficiency was considered as serum 25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL (50 nmol/L). RESULTS: The overall prevalence rate of vitamin D deficiency in the elderly was 62.1%. The factors such as female, obesity, metabolic syndrome, current smoker, and skipping breakfast were positively associated with vitamin D deficiency, but high intensity of physical activity and more than 9 hours of sleep duration were negatively associated with vitamin D deficiency (all P < 0.05). CONCLUSIONS: It is important that health professions know that the factors proved in this study are connected to vitamin D deficiency thus provide information and intervention strategies of vitamin D deficiency to old aged people.
Aged*
;
Aging
;
Breakfast
;
Chronic Disease
;
Female
;
Health Occupations
;
Humans
;
Independent Living*
;
Korea*
;
Metabolism
;
Motor Activity
;
Nutrition Surveys
;
Obesity
;
Prevalence
;
Risk Factors
;
Vitamin D Deficiency*
;
Vitamin D*
;
Vitamins*

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